Sridharan Meera, Go Ronald S, Willrich Maria A V
Division of Hematology, Rochester, MN.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Mayo Clin Proc Innov Qual Outcomes. 2022 Sep 17;6(5):458-464. doi: 10.1016/j.mayocpiqo.2022.03.005. eCollection 2022 Oct.
One of the treatment options for complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome, is the administration of the C5 complement inhibitor eculizumab. In vivo studies have reported a complete complement blockade with eculizumab serum concentrations above 50 μg/mL in the case of atypical hemolytic uremic syndrome. The eculizumab trough levels and C5 functional activity were monitored in patients with CM-TMA being treated with eculizumab. For those with eculizumab trough concentrations of more than 100 μg/mL, the frequency of eculizumab 1200-mg doses was decreased. In this article, we describe the pharmacologic monitoring data with the use of C5 functional activity and mass spectrometric assessments of eculizumab to allow for a tailored eculizumab schedule for 10 patients with CM-TMA. In 9 out of 10 (90%) patients with a standard administration schedule, eculizumab trough concentrations were more than 100 μg/mL. At the time of the last eculizumab follow-up (median, 250 days; range, 85-898 days), the interval between eculizumab infusions was extended to every 3-6 weeks for 8 patients; no disease relapse was found with the modified dosing interval. Altering the administration of maintenance eculizumab from every 2-3 weeks to 3-6 weeks yields a savings of $78,185 per patient for a 6-month eculizumab treatment course. Although larger standardized cohorts are necessary to confirm these findings, our data suggest that monitoring eculizumab levels in conjunction with C5 assessment allows for safe modification of eculizumab dosing and results in considerable cost savings.
补体介导的血栓性微血管病（CM-TMA），也称为非典型溶血尿毒综合征，其治疗选择之一是给予C5补体抑制剂依库珠单抗。体内研究报告称，在非典型溶血尿毒综合征的情况下，依库珠单抗血清浓度高于50μg/mL时可实现完全补体阻断。对接受依库珠单抗治疗的CM-TMA患者监测了依库珠单抗谷浓度和C5功能活性。对于依库珠单抗谷浓度超过100μg/mL的患者，减少了依库珠单抗1200mg剂量的给药频率。在本文中，我们描述了使用C5功能活性和依库珠单抗质谱评估的药理监测数据，以便为10例CM-TMA患者制定个性化的依库珠单抗给药方案。在10例采用标准给药方案的患者中，有9例（90%）依库珠单抗谷浓度超过100μg/mL。在依库珠单抗末次随访时（中位数为250天；范围为85-898天），8例患者的依库珠单抗输注间隔延长至每3-6周一次；调整给药间隔后未发现疾病复发。将依库珠单抗维持给药从每2-3周改为每3-6周，对于为期6个月的依库珠单抗治疗疗程，每位患者可节省78185美元。尽管需要更大规模的标准化队列来证实这些发现，但我们的数据表明，结合C5评估监测依库珠单抗水平可安全调整依库珠单抗剂量，并可节省大量成本。
